Factors capable of inhibiting synaptic transmission and increasing spike threshold in cultured mammalian neurons and frog spinal cord have been shown to be present in human sera during acute exacerbations of multiple sclerosis. The first objective is to determine, using a voltage-clamp system for single frog sciatic nerve fibers and microelectrode techniques for frog spinal motorneurons, the mechanism of action of such neurotoxic substances on excitable and synaptic membranes, and whether they are similar or different. We will then identify the neurotoxic components of active sera using combined electrophysiological and immunological techniques. Concurrently with these determinations we will establish a system capable of detecting small differences in the level of circulating neurotoxin, and follow selected multiple sclerosis patients longitudinally throughout the course of their disease so as to determine the extent to which variations in neurotoxin levels are correlated with the clinical course. Finally we shall select certain patients of a prospective study designed to assess the utility of an assay of neurotoxin activity as a diagnostic aid in this disease.